Apokyn

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Apokyn

INDICATIONS

APOKYN® (apomorphine hydrochloride injection) is
indicated for the acute, intermittent treatment of hypomobility, “off” episodes
(“end-of-dose wearing off” and unpredictable “on/off” episodes) in patients
with advanced Parkinson's disease. APOKYN has been studied as an adjunct to
other medications [see Clinical Studies].

DOSAGE AND ADMINISTRATION

Important Administration Instructions

APOKYN is indicated for subcutaneous administration only [see
WARNINGS AND PRECAUTIONS] and only by a multiple-dose APOKYN Pen with
supplied cartridges. The initial dose and dose titrations should be performed
by a healthcare provider. Blood pressure and pulse should be measured in the
supine and standing position before and after dosing.

A caregiver or patient may administer APOKYN if a healthcare
provider determines that it is appropriate. Instruct patients to follow the
directions provided in the Patients Instructions For Use. Because the APOKYN
Pen has markings in milliliters (mL), the prescribed dose of APOKYN should be
expressed in mL to avoid confusion.

Visually inspect the APOKYN drug product through the
viewing window for particulate matter and discoloration prior to
administration. The solution should not be used if discolored (it should be
colorless), or cloudy, or if foreign particles are present. Rotate the
injection site and use proper aseptic technique [see HOW SUPPLIED/Storage
and Handling and PATIENT INFORMATION].

Premedication And Concomitant Medication

APOKYN should be initiated with the use of a concomitant
antiemetic [see WARNINGS AND PRECAUTIONS]. Oral trimethobenzamide (300
mg three times a day) should be started 3 days prior to the initial dose of
APOKYN and continued at least during the first two months of therapy.

Based on reports of profound hypotension and loss of
consciousness when apomorphine was administered with ondansetron, the
concomitant use of apomorphine with drugs of the 5HT3 antagonist class
including antiemetics (for example, ondansetron, granisetron, dolasetron,
palonosetron) and alosetron are contraindicated [seeCONTRAINDICATIONS].

Dosing Information

The recommended starting dose of APOKYN is 0.2 mL (2 mg).
Titrate on the basis of effectiveness and tolerance, up to a maximum
recommended dose of 0.6 mL (6 mg) [see Clinical Studies].

There is no evidence from controlled trials that doses
greater than 0.6 mL (6 mg) gave an increased effect and therefore, individual
doses above 0.6 mL (6 mg) are not recommended. The average frequency of dosing
in the development program was 3 times per day. There is limited experience
with single doses greater than 0.6 mL (6 mg), dosing more than 5 times per day
and with total daily doses greater than 2 mL (20 mg).

Begin dosing when patients are in an “off” state. The
initial dose should be a 0.2 mL (2 mg) test dose in a setting where medical
personnel can closely monitor blood pressure and pulse. Both supine and
standing blood pressure and pulse should be checked pre-dose and at 20 minutes,
40 minutes, and 60 minutes post-dose (and after 60 minutes, if there is
significant hypotension at 60 minutes). Patients who develop
clinically significant orthostatic hypotension in response to this test dose of
APOKYN should not be considered candidates for treatment with APOKYN.

If the patient tolerates the
0.2 mL (2 mg) dose, and responds adequately, the starting dose should be 0.2 mL
(2 mg), used on an as needed basis to treat recurring “off” episodes. If
needed, the dose can be increased in 0.1 mL (1 mg) increments every few days on
an outpatient basis.

The general principle guiding
subsequent dosing (described in detail below) is to determine that the patient
needs and can tolerate a higher test dose, 0.3 mL or 0.4 mL (3 mg or 4 mg,
respectively) under close medical supervision. A trial of outpatient dosing may
follow (periodically assessing both efficacy and tolerability), using a dose
0.1 mL (1 mg) lower than the tolerated test dose.

If the patient tolerates the
0.2 mL (2 mg) test dose but does not respond adequately, a dose of 0.4 mL (4
mg) may be administered under medical supervision, at least 2-hours after the
initial test dose, at the next observed “off” period. If the patient tolerates
and responds to a test dose of 0.4 mL (4 mg), the initial maintenance dose should
be 0.3 mL (3 mg) used on an as needed basis to treat recurring “off” episodes
as an outpatient. If needed, the dose can be increased in 0.1 mL (1 mg)
increments every few days on an outpatient basis.

If the patient does not
tolerate a test dose of 0.4 mL (4 mg), a test dose of 0.3 mL (3 mg) may be
administered during a separate “off” period under medical supervision, at least
2-hours after the previous dose. If the patient tolerates the 0.3 mL (3 mg)
test dose, the initial maintenance dose should be 0.2 mL (2 mg) used on an as
needed basis to treat existing “off” episodes. If needed, and the 0.2 mL (2 mg)
dose is tolerated, the dose can be increased to 0.3 mL (3 mg) after a few days.
In such a patient, the dose should ordinarily not be increased to 0.4 mL (4 mg)
on an out-patient basis.

Dosing In Patients With Hepatic
Impairment

If a single dose of APOKYN is
ineffective for a particular “off” period, a second dose should not be given
for that “off” episode. The efficacy of the safety of administering a second
dose for a single “off” episode has not been studied systematically. Do not
administer a repeat dose of APOKYN sooner than 2 hours after the last dose.

Patients who have an
interruption in therapy of more than a week should be restarted on a 0.2 mL (2
mg) dose and gradually titrated to effect and tolerability.